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IVERMECTIN

IVERMECTIN USE - MODE OF ACTION - POISONING

Ivermectin has saved countless animals from the pain of mites and parasites.

Ivermectin is used to rid animals and humans of many internal and external (blood sucking) parasites . Lice and hair mites which do not ingest the blood of the host are not affected by ivermectin administered orally or by injection (See notes at bottom of page).

In guinea pigs, ivermectin is the drug of choice for treatment of the selnick mite. Trixacarus caviae, a burrowing sarcoptid mite, is a member of the arachnid family. Transmission occurs primarily through direct contact with infested animals although eggs can be carried to them inadvertently. Mites will seldom leave the host unless brushed onto the bedding or as a result of overpopulation or the death of the host. With no host, they will usually die within 3 weeks. However the eggs, which are laid in burrows in the skin, may survive off the host for long periods of time. These species specific microscopic mites cause unbearable itchiness for the animal and can result in thinning and/or patchy loss of hair and scurfing of the skin (may resemble dandruff). Severe infestations can be life threatening. The most serious infestations occur in the young and ill older animals subject to stress and poor environmental conditions. The response in healthy animals, perhaps due to grooming or suppressed immune response is less severe. "Maximal parasite load is reached approximately 1 month after infection (Rothwell et al., 1991) then slowly regresses if left untreated. Mortality is common in some reports." (Harkness and Wagner)

A macrolide antibiotic licensed for use in 1984, ivermectin is produced from a fungus first isolated from a soil sample in Japan - Streptomyces avermitilis. The American Board of Veterinary Toxicology (ABVT) describes its mode of action as:

"An agonist for the neurotransmitter gamma-aminobutyric acid (GABA). GABA is a major inhibitory neurotransmitter. In mammals, GABA-containing neurons and receptors are found in the Central Nervous System; while in arthropods and nematodes GABA is found primarily in the Peripheral Nervous System (neuromuscular junction). This difference in location of GABA receptor may be the reason for the large margin of safety of ivermectin-containing products in mammals [my emphasis]. The binding of ivermectin to a neuronal membrane increases the release of GABA. GABA binds to the GABA receptor-chloride channel complex of postsynaptic neuronal membranes causing an influx of chloride ions. The influx of chloride ions hyperpolarize the neuronal membrane making them less excitatory and decreasing nerve transmission. The hyperpolarization of neuronal membranes (at the NMJ) mediate a flaccid paralysis in arthropods and nematodes."

Ivermectin has been cleared for use in humans, swine and cattle, horses, and sheep. On March 1997, Stromectol (also ivermectin) was approved for use in humans as a treatment for infection with nondisseminated intestinal threadworm (strongyloidiasis). "Off-label" use of this product has been suggested for head lice in humans and scabies in immuno-compromised patients such as HIV/AIDS patients.

A fascinating article by Andy CRUMP and Satoshi OMURA, Ivermectin, ‘Wonder drug’ from Japan: the human use perspective, describes how ivermectin "was quickly discovered to be ideal in combating two of the world’s most devastating and disfiguring diseases which have plagued the world’s poor throughout the tropics for centuries." Ivermectin has been heralded as one of the most important drugs of all time.

Ivermectin is usually administered in two or more doses, by injection or orally, spaced 7 to 14 days apart (see vet) and can even be used topically (generally at 0.5mg/kilo). Dosage varies slightly from one species to another (0.2 mg/kilo for cattle and horses, 0.3 mg/kilo swine, 0.2 mg/kilo sheep, much less for dogs and cats). Overdoses given by "well-intentioned, yet uninformed owners" can produce toxic side effects, especially in susceptible breeds. The ABVT claims that "Any species may be affected if the dose is large enough to penetrate the Blood-Brain-Barrier".

TOXICITY

The ABVT list the clinical signs of poisoning as:

mydriasis -- [excessive dilatation of the pupil of the eye, as the result of disease, drugs or the like]

depression

coma

tremors

ataxia -- [loss of coordination of the muscles, especially of the extremities]

stupor

emesis -- [vomiting]

drooling

death

It is thought there are no long term effects from mild overdoses. Animals showing reactions following recommended doses should not receive further treatment using ivermectin.

Use of this product in guinea pigs is considered "off-label". However, given the efficacy of the drug and apparent safety in proper doses, ivermectin has been studied on guinea pigs to determined safe doses and methods of administration by the research community. Their results offer guidelines for its use and are routinely listed in a variety of medical reference books on guinea pigs, enabling vets to properly treat our pets.

Is important to note that there are yearly reports of deaths of cattle, horses, dogs, cats, rabbits, etc. from the topical, oral and intravenous use of ivermectin (two of which are included here) (FDA) (FDA) . It is not known, but expected, that these deaths may be the result of incorrect dose or use.

LICE

Lice treatment is only listed for cattle and swine. In cattle treated by injection, the following lice, identified as "sucking lice", are listed (FDA - NADA 128-409) :

Linognathus vituli

Haematopinus eurysternus

Solenopotes capillatus

In cattle treated by topical application (along the topline in a narrow strip extending from the withers to the tailhead) at a rate of 0.5mg/kilo, lice identified as "sucking and biting lice" are listed (FDA - NADA 140-841) :

"Control of the following tick will be provided by interfering with engorgement with blood and completion of the reproductive portion of the life cycle by newly acquired young adult females during the period of ivermectin delivery. However, larvae, nymphs and adult males, as well as young adult females already on the host at the time of treatment and actively in the engorgement process, may not be visibly affected." Ivermectin applied topically will also provide some control of the horn fly, Hematobia irritans(adults): in heavily infested animals, good control for 1 to 2 weeks; in lightly infested animals they may be eradicated. (FDA - NADA 128-409)

Applied topically, ivermectin may be an effective control of the biting lice, gliricola porcelli (the slender guinea pig louse) and the less common gyropus ovalis (the oval guinea pig louse). Ivermectin administered topically is absorbed into the body of the animal; many of the same internal parasites treated by injection are also treated by the topical application of ivermectin. Ivermectin remains an apparently a reliable method of treating for mange mites (Trixacarus caviae), according to a study cited by Harkness and Wagner, by McKellar et al. (1992) using 0.5 mg/kg topically and repeating 7 days later.

PREGNANCY AND THE YOUNG

Horses:"No adverse effects on reproduction were seen in these trials and it was concluded that ivermectin may be used safely in breeding stallions and in pregnant mares....There are insufficient data to determine safety of ivermectin liquid in foals less than 4 months old." (FDA - NADA 140-439)

Cattle: Some ivermectin products are for use in ruminating cattle of at least 12 weeks of age (not the very young) . Data presented on subcutaneous administration of ivermectin showed no adverse effects on breeding cattle. Applied topically, the concentration of ivermectin in the blood was significantly lower than the concentration of ivermectin applied subcutaneously in the blood, supporting the claim that topical application is also safe in breeding cattle. (FDA - NADA 140-841)

Sheep: "No stillbirths occurred in either group and no deformities were found in any lambs. Ivermectin was concluded to have had no effect on these pregnant ewes or their lambs." (FDA - NADA 131-392)

Dogs: "There were no clinical signs of toxicity among pregnant female dogs receiving ivermectin. Average maternal body weight gains were not affected by ivermectin treatment." (note the low doses used) (FDA - NADA 138-412)Cats: "Ivermectin, administered in this chewable dosage form, is safe when administered to kittens at the label dosage of 24 mcg/kg body weight. There were no statistically significant effects of treatment on birth weight or weaning weight of kittens, on numbers of litters with mortalities or abnormalities, on total litter size, percent born alive and percent weaned, or on weight gains of male cats.... Labeling restricts this drug to use by or on the order of a licensed veterinarian because professional expertise and proper diagnosis are required to determine the existence of hookworm and/or heartworm infections." (FDA - NADA 141-078)

Rats, rabbits, and mice are referred to when evaluating the safety of ivermectin in horses: "Ivermectin has been shown to be teratogenic in rats, rabbits, and mice at or near maternotoxic dose levels. At these high doses, evidence of a teratogenic effect is limited to cleft palate that occurs at a low frequency in all three species and clubbing of the forepaws which occurs only in rabbit fetuses. Mice are the most sensitive species to the effects of ivermectin with maternotoxicity at a dose of 200 mcg/kg/day and teratogenicity at 400 mcg/kg/day. In rabbits 6000 mcg/kg/day was maternotoxic and teratogenic, and teratogenicity was also evident at a dose of 3000 mcg/kg/day. The threshold for both maternotoxicity and teratogenicity in rats was 10,000 mcg/kg/day." (FDA - NADA 140-439)

FDA INFORMATION

Due to occasionally changing addresses (dead links), the author has opted to include at this site the FDA records referred to on this page. Information at the FDA is not copywrited and the public may freely reproduce and use this information. The FDA appreciates being informed about the use of Website materials. Contact FDA, HFI-50, Rockville, MD 20857 or e-mail webmail@oc.fda.gov.

A link to the search feature is included here to enable readers to determine if any reports have changed, although unlikely, due to selection of documents (original applications and yearly reports of deaths). You are encouraged to search the site for further information. Entering a report title like "fda/NADA 140-439" should link you to the original document in most cases.